This competing continuation application requests support to train five post-resident (MD or MD/PhD) or PhD scientists for investigative careers in reproductive research. Equipping a small but well-qualified subset of MD and PhD scientists who can pursue basic and pathophysiological studies of reproductive processes in children, adolescents and adults is essential to the nation's current and future health care needs. Indeed, infertility and other reproductive disorders are a problem for one out of every 12 couples in the United States. At the same time, about half of the pregnancies that do occur are unplanned. The consequences of these difficulties - emotional, social, economic - have a profound impact on the families of affected individuals as well as society. Our training program develops biomedical scientists who can meet these challenges by equipping them with the tools of cellular and molecular biology so they can uncover the mechanisms of basic reproductive processes. Research and didactic experiences are tailored to accommodate trainees from diverse professional and academic backgrounds. Supplemental instruction is offered, including courses in biostatistics, cell biology, recombinant DNA technology and clinical investigation, with the goal of producing well-rounded interdisciplinary scientists who can contribute important new insights on the mechanisms that regulate reproductive disorders in both children and adults. Interdisciplinary research training is achieved through interactions with preceptors who hold appointments in basic and clinical departments at the University and who share a common research interest in one or more aspects of infertility and other reproductive disorders. All mentors hold faculty appointments in the School of Medicine or College of Arts and Sciences, are funded by at least one research grant, and have experience in training postdoctoral scientists for productive careers. The institutional environment offers a rich mix of core facilities, seminars, visiting professors, and conferences that fosters highly interactive and stimulating exchanges among trainees and mentors. The broad themes of faculty research programs include: the molecular analysis of sperm-egg fusion, signal transduction mechanisms from membrane receptors, protein kinases, nuclear transcription factors and transcriptional regulation, neuroendocrine control mechanisms in reproduction, molecular control of spermatogenic cell development and differentiation, immune mechanisms of tolerance and autoimmunity to sperm-egg antigens, and the etiology of polycystic ovarian syndrome. Continued training of young internists, neurologists, pediatricians, obstetricians, and basic scientists in cellular and molecular approaches to infertility and other reproductive disorders is consistent with the tradition and commitment to foster a close link between basic and clinical investigators that has been a productive common ground for training MD and PhD scientists at the University of Virginia.